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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: (Richard Gebkin, PM 10, (703) 305-6701] INSTRUCTIONS: Please utilize this outline inpreparing the pesticide petition. In cases where the outline element does notapply, please insert "NA-Remove"and maintain the outline. Please do not changethe margins, font, or format inyour pesticide petition. Simply replace the instructions that appear in green, i.e., "(insert company name]," with the informationspeciflc to youraction. TEMPLATE: Gowan Company [Insert petition number] EPAhas received a pesticidepetition ((insert petition number]) from Gowan Company, LLC,P.O. Box 556 Yuma,AZ 85366proposing,pursuant to section 4()8(d) ofthe Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFRpart 180. (Options (pick one) 1. by establishing a tolerance forresidues of
Hexj'thiazox, (trans-5-(4-chlorophenyl)-N-cyclohexyl-4-methyl-2- oxothiazolidine-3-carboxamide) in or on theraw agricultural commodit\' sugar beet, , . tops at 1.5 ppm, sugar beet, roots at 0.15 ppm and processed commodities, sugar beet, molasses at0.21 ppm and sugar beet,dried pulp at 0.60ppm. EPAhas .****• determined that thepetition contains data or informationregarding the elements set forth **" i • • in section 408 (d)(2) of FDDCA;however, EPAhas not fully evaluated the sufficiency ,,,, * ofthe submitted data at this time or whetherthedata supports granting ofthepetition. *,,* Additional data maybeneededbefore EPArules on the petition.
A.Residue Chemistry ••••••

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1.Plant metabolism. The nature ofthe residues in plants is adeqnately understood for purposes ofthis tolerance petition. Metabolism studies in fruit crops, •* radish, tea and corn have been completed. The Agency has determined that the residues ofconcern are hex\'thiazox and its metabolites containing the (4-chlorophenyl)-4-methyl-2-oxo-3-thiazolidine moiet\* calculated as the stoichiometric equivalent ofhesythiazox.2.Analytical method.The basic analytical method was previously reviewed by

the Agency in association with the establishment ofthe current tolerances with registrations of multiple commodities.The methods used in a new sugar beet raw agricultural commodities study aredescribed fully in the study report which is submitted concurrently with this petition. 3.Magnitude ofresidues. ANew Magnitude ofthe Residue data have been generated on sugar beet in EPA Regions 7 (one trial), 8(one trial), 9 (one trial),10 (two trials), and 11 (one trial) tosupport regional registration. One sugar beet decline trial was conducted in EPA Regions 10.Six trials were conducted on sugar beet during the 2013 (three trials) and 2014 (three trials) growing seasons.The treated plots received one foliar broadcast application of Onager®lE Miticide at 0.1875 lb ai/A (equal to0.210kg ai/ha) ± 5% applied 45 (±1) days before harvest (DBH). At Trial -06, an additional exaggerated 5x rate treated plot was established to generate sugar beetroots for the processing phase. This plot received one 5xrate application of Onager® IE Miticide at 0.9375 lb ai/A (equal to 1.05 kg ai/ha) ±5% applied 45 (±1) DBH. A single untreated control and duplicate treated RAC samples were harvested by hand at each location at normal crop maturity nominally 45 (44-46 day range) days after the application (DAA). At the decline site,additional treated RAC samples were collected 38, 59, and 66 DAA. The results from these trials show that after oneapplication ofOnager® IE Miticide at 0.1875 lb ai/A (0.210kg ai/ha) ± 5% residues ofhexvthiazox ranged from 0.208 to 0.614ppm (mean = 0.459ppm ± 0.128) on twelve sugar beet top RAC samples collected 44-46 DAA and from <LOQ (0.00829) to 0.0597 ppm (mean = 0.0271ppm ± 0.0150) on twelve sugar beet root RAC samples collected 44-46 DAA. The results from the processing study show that after one 5x rate application of Onager® IE Miticide at 0.9359 lb ai/A (equal to 1.049kg ai/ha), mean residues of hexj'thiazox in/on whole sugar beet roots collected immediately prior to processing;,,,;, was 0.311ppm, collected 45 DAA. Mean residues ofhexvthiazox in refined sugar, molasses, and dried pulp was 0.0425ppm, 0.427ppm, and 1.24 ppm, respectively. A,,,,* comparison of the hexjthiazox residues in the RAC with those in the processed • fractions (refined sugar, molasses, and dried pulp) indicated that the residues of hexvthiazox in sugar beet refined sngar, molasses, and dried pulp have **** •• concentration factors of approximately <lx, 1.4x, and 4.Ox, respectively. • •

B. ToxicologicalProfile 1.Acutetoxicity. Abattery ofacute toxicity studies places technical grade hexythiazox in Toxicity' Category IVfor acute oral toxicity (LDso > 5,000 mg/kg), Categorv HI for acutedermal toxicitj' (LDso >5,000 mg/kg), Category HI for acute inhalation toxicity (LCso >2.0 mg/L), Category III for primary eye irritation (showed mild irritation (reddened conjunctiva) and Category IV for dermal irritation (non irritant). Hexythiazox is a non-sensitizer. * ••• • • •• •2. Genotoxicity.A number of mutagenicity studies wereconducted. Theseare

a mammalian erythrocyte micronucleus test [IVIRID 45480101], a mammalian cell forward gene mntation assay PVIRID00155154], a rat primary hepatocyte unscheduled DNA synthesis assay [MRID 00156893], a clastogenic evaluation in an in vitro cytogenetic assay measuring chromosomal aberration in Chinese hamster ovary cells [MRID 00156894], and an Ames study withSalmonella [MRID 44955710]. All these mutagenicity tests were negative. 3. Reproductive anddevelopmental toxicity.In a developmental toxicity study with rats [MRID 00147578], the fetotoxicity NOEL was 240 mg/kg/day, and the compound was not embryotoxic at the highest dose tested, 2160 mg/kg/day. In a developmental toxicity study with rabbits [MRID 00146555], no developmental toxicity' was observed at the highest dose tested, 1080 mg/kg/day. In a twogeneration reproduction study with rats [MRID 00147578 and 00151360], no reproductive effects were observed at 2400ppm in the diet (^110 and >139 mg/kg/day, males and females, respectively). It is concluded that the NOEL for developmental and reproductive effects is greater than 10 times the chronic NOEL.

4. Subchronic toxicity.In a 1-month feeding study in dogs, the NOAEL was 1.75 mg/kg/day and the LOAEL was12.5 mg/kg/day, based on increased liver and adrenal weights. 5. Chronic toxicity. In a 1-year feeding study in dogs, the NOAEL was 2.5 mg/kg/day and the LOAEL was 12.5 mg/kg/day, based on increased alkaline phosphatase, increased adrenal and liver weights, and liver and adrenal lesions. In a carcinogenicity study in mice, the NOAEL was 36 mg/kg/day and the LOAEL was 215 mg/kg/day. Effects were decreased bodweight in males and increased hepatocellular carcinomas and combined adenoma/carcinomas.
In a chronic feeding/carcinogenicity study inrats, the NOAEL (systemic) was 26 mg/kg/day and the LOAEL (systemic) was 180 mg/kg/day based on decreased body weight gain and increased liver weights in both sexes. 'im*
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• • •••••• A 2009 report from the Cancer Assessment Review Committee (CARC) (September#,••••• 02,2009, PC Code 128849,TXR 0055255) noted that the NOAEL of 2.5 mg/kg/day,*••••* *.•* from the one year toxicity studyin dogs, used in establishing the chronic reference •**•*• dose (RfD) is approximately 65-fold lower than the lowest dose(163 mg/kg/day) that' , induced tumors. Thus, the chronicRfD of0.025 mg/kg/day would be protective of all chronic effects including potential carcinogenicity ofhexythiazox. The CARC concluded that the evidence as a whole was not s trong enough to warrant the use of,* !*• a linear low dose extrapolation model applied to the animal data (Ql*) for a quantitative estimation of human risk, as had been previously assessed in October 16,1998, [63.FR55540].
6.Animal metabolism. The metabolism ofhexvthiazox has been studied ingoats, hens and rats. Metabolic pathways in the animal aresimilar to those in

plants.7. Metabolite toxicology. There are no metabolites oftoxicological concern based on a differential metabolism between plants and animals. 8. Endocrine disruption. Information concerning possible endocrineeffects of hex}'thiazox similar to effects produced by a naturally occurring estrogen, or other endocrineeffects is available from the two-generation rat reproduction study, the rat and rabbit developmental studies and the rat and dog chronicstudies. Thereis no evidence from thesestudies that hexjthiazox induces estrogenicor other endocrine effects. C.AggregateExposure 1. Dietary exposure. Dietary Exposure from food. A dietary risk assessment for all registered crops has been completed by the Agency (Federal Register, July 17, 2013, pages 42693-42699). 1.Food. Acute Exposure. No acute endpoint has been identified in the toxicological studies for hexythiazox; therefore, a quantitative acutedietary exposure assessment isunnecessary. Chronic Exposure.The proposed regional tolerances for hexj thiazoxin sugar beet will not add to dietary risk. A tier 1chronic assessment shows employing tolerance residue values, theassumption of 100% crop treated and default processing factors shows that the maximally exposed subpopulation (children 1-2 years old) utilized 93.1% ofthe RfD. ii.Drinking water. The Agency has previously used screening level surface water exposure models in dietaiy exposure analysis and risk assessment for hexythiazox in drinking water. Based on the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS), the estimated drinking water concentration (EDWC) of hexythiazoxfor chronicassessment was estimated to be* 4.31parts per billion (ppb). (Federal Register, Julv 17, 2013, pages 42693-42699) 2. Non-dietary exposure. EPA has previously determined that potential residential exposures to hex^'thiazox arebelow levels ofconcern. **** •• «**• • •• • D. CumulativeEffects • • • EPA has not found that hexythiazox sharesa common mechanism of toxicity* with any other substances. • • •

E. SafetyDetermination 1. U.S.population. Acute risk. No adverse effect resulting from a single oral exposure to hexythiazox has been identified, thus hexythiazox is not expected to posean acute risk.

Short-and intermediate term risk. EPA has previously concluded that there are no short term or intermediate term risks ofconcern from exposure to hexjihiazox. Chronic risk. The proposed regional tolerances for hexythiazox in sugar beet will not add to dietary' risk. A tier 1chronic assessmentshows employing tolerance residue values, theassumption of 100% crop treated and default processing factors shows that the maximally exposed subpopulation (children 1-2years old) utilized 93.1% ofthe RfD. Chronic residential exposureto the residues ofhexythiazox is not expected. 2. Infants andchildren. EPA previously has determined that reliable data show thesafety ofinfants and children would be adequately protected ifthe EQPA SFwere reduced to IX. Based on these risk assessments, it can be concluded that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to hexythiazox residues.
F.International Tolerances There are nointernational maximum residue levels established for hexythiazox on sugar beet.

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